Metabolic adaptations in cancer stem cells: A key to therapy resistance.

Cancer stem cells (CSCs) are a subset of tumor cells that can initiate and sustain tumor growth and cause recurrence and metastasis. CSCs are particularly resistant to conventional therapies compared to their counterparts, owing greatly to their intrinsic metabolic plasticity. Metabolic plasticity allows CSCs to switch between different energy production and usage pathways based on environmental and extrinsic factors, including conditions imposed by conventional cancer therapies. To cope with nutrient deprivation and therapeutic stress, CSCs can transpose between glycolysis and oxidative phosphorylation (OXPHOS) metabolism. The mechanism behind the metabolic pathway switch in CSCs is not fully understood, however, some evidence suggests that the tumor microenvironment (TME) may play an influential role mediated by its release of signals, such as Wnt/ß-catenin and Notch pathways, as well as a background of hypoxia. Exploring the factors that promote metabolic plasticity in CSCs offers the possibility of eventually developing therapies that may more effectively eliminate the crucial tumor cell subtype and alter the disease course substantially.

Surface Markers for the Identification of Cancer Stem Cells.

Cancer stem cells have genetic and functional characteristics which can turn them resistant to standard cancer therapeutic targets. Identification of these cells is challenging and is done mainly by detecting the expression of antigens specific to stem cells. Currently, there is a significant number of surface markers available which can detect cancer stem cells by directly targeting the specific antigens present in cells. These markers possess differential expression patterns and sub-localizations in cancer stem cells compared to nonneoplastic and somatic cells. In addition to these biomarkers, multiple analytical methods and techniques, including functional assays, cell sorting, filtration approaches, and xenotransplantation methods, are used to identify cancer stem cells. This chapter will overview the functional significance of cancer stem cells, their biological correlations, specific markers, and detection methods.

Antitumor Activity of a Lectin Purified from Punica granatum Pulps against Ehrlich Ascites Carcinoma (EAC) Cells.

BACKGROUND: Lectins are carbohydrate-binding proteins with various pharmacological activities, such as antimicrobial, antidiabetic, antioxidant, and anticancer. Punica granatum fruit extract has traditional uses, however, the anti-cancer activity of purified lectin isolated from P. granatum pulp is yet to be reported. OBJECTIVE: The goals of this study are purification, characterization of the lectin from P. granatum, and examination of the purified lectin's anticancer potential. METHODS: Diethylaminoethyl (DEAE) ion-exchange chromatography was used to purify the lectin, and SDSPAGE was used to check the purity and homogeneity of the lectin. Spectrometric and chemical analysis were used to characterize the lectin. The anticancer activity of the lectin was examined using in vivo and in vitro functional assays. RESULTS: A lectin, designated as PgL of 28.0 ± 1.0 kDa molecular mass, was isolated and purified from the pulps of P. granatum and the lectin contains 40% sugar. Also, it is a bivalent ion-dependent lectin and lost its 75% activity in the presence of urea (8M). The lectin agglutinated blood cells of humans and rats, and sugar molecules such as 4-nitrophenyl-α-D-manopyranoside and 2- nitrophenyl -ß- D-glucopyranoside inhibited PgL's hemagglutination activity. At pH ranges of 6.0-8.0 and temperature ranges of 30°C -80°C, PgL exhibited the highest agglutination activity. In vitro MTT assay showed that PgL inhibited Ehrlich ascites carcinoma (EAC) cell growth in a dose-dependent manner. PgL exhibited 39 % and 58.52 % growth inhibition of EAC cells in the mice model at 1.5 and 3.0 mg/kg/day (i.p.), respectively. In addition, PgL significantly increased the survival time (32.0 % and 49.3 %) of EAC-bearing mice at 1.5 and 3.0 mg/kg/day doses (i.p.), respectively, in comparison to untreated EAC-bearing animals (p < 0.01). Also, PgL reduced the tumor weight of EAC-bearing mice (66.6 versus 39.13%; p < 0.01) at the dose of 3.0 mg/kg/day treatment. Furthermore, supplementation of PgL restored the haematological parameters toward normal levels deteriorated in EAC-bearing animals by the toxicity of EAC cells. CONCLUSION: The results indicated that the purified lectin has anticancer activity and has the potential to be developed as an effective chemotherapy agent.